The goals of this research project are directed toward a better understanding of the electrophysiologic mechanisms underlying the rhythmic disturbances in the ischemic heart which lead to ventricular fibrillation in the conscious, ambulatory animal or to reentrant arrhythmias in response to programmed electrical stimulation. The electrophysiologic testing techniques and the animal model of spontaneous ventricular fibrillation will permit us to critically evaluate the various classes of antiarrhythmic drugs with respect to their ability to prevent life threatening arrhythmias and/or sudden coronary death. Because of the similarity in response to the clinical use of programmed electrical stimulation, the exprimental canine model offers a promising approach to the evaluation of antiarrhythmic and antifibrillatory drugs. The studies proposed in the chronically ischemic canine heart will have great potential in the preclinical evaluation of pharmacologic interventions for prophylactic use in patients at high risk of developing out-of-hospital ventricular fibrillation. The studies for the current year will concentrate on an evaluation of antiarrhythmic agents belonging to Class III and IV which will be compared to some of the newer Class I drugs for their efficacy in preventing ventricular fibrillation in the dog with chronic myocardial ischemic injury.